Table 1.

Candidate mechanisms for chemotherapy-induced cognitive changes

Mechanism	Prediction	Findings relevant to cognition in cancer	Candidate genes*	Refs
Blood–brain barrier	Patients with one or more alleles associated with less efficient efflux pumps will be more likely to have cognitive problems before and after treatment		Multidrug resistance 1 (MDR1, which encodes P-glycoprotein (P-gp)) Organic anion transporting polypeptide (Oatp)	32-34
DNA damage	Cognitive changes will be associated with the degree of DNA damage Patients with higher levels of DNA damage before treatment will be more likely to meet criteria for cognitive impairment Patients with one or more alleles associated with lower efficiency DNA-repair mechanisms will be more likely to have cognitive problems before and after treatment		8-oxoguanine DNA glycosylase (OGG1) Apurinic/apyrimidinic endonuclease 1 (APEX1) X-ray repair cross complementing protein 1 (XRCC1)	38,55
Telomere length	Lower telomere length and telomerase activity will be associated with poor cognitive performance		DDX11 (a DNA helicase)	57
Cytokine regulation	Higher levels of proinflammatory cytokines (for example, interleukin 1 (IL1), IL2, IL6, IL10 and tumour necrosis factor-α (TNFα)) will be associated with greater likelihood of cognitive problems, both before and after treatment Patients with one or more alleles associated with cytokine deregulation will be more likely to have cognitive problems before and after chemotherapy	Cognitive side effects of interferon and interleukin therapy Higher levels of IL6 are associated with reduced executive function	IL1 IL6 TNFα	23,66,70,71,79
Neural repair	Apolipoprotein E (APOE) E4 allele carriers will have more cognitive problems after chemotherapy Brain-derived neurotrophic factor (BDNF) Val66Met carriers will have more cognitive problems after chemotherapy	The APOE E4 allele has been associated with poorer cognitive performance in cancer survivors	APOE E4 allele BDNF Val66Met	80,86,89
Neurotransmitters	Patients with one or more alleles associated with decreased neurotransmitter activity will be more likely to have cognitive problems before and after treatment	Preliminary data suggest that the valine allele is associated with poorer cognitive performance in cancer survivors	Catechol-O-methyltransferase (COMT)	89,93,96

^*Examples of candidate genes are provided. See the references for a more extensive list.